Definitions UC Inflammation confined to mucosa Inflammation confined to mucosa Starting in rectum Starting in rectum May involve entire colon May involve entire colon Crypt abscess Crypt abscess Rare Rare Rectal sparing Rectal sparing Discontinuous Discontinuous Only proctitis Only proctitis Crohn’s Superficial ulcer to submucosa, muscularis and serosa Superficial ulcer to submucosa, muscularis and serosa Transmural inflammation Transmural inflammation Any portion of the alimentary tract Any portion of the alimentary tract Mouth to anus Mouth to anus Fistulas Fistulas Granulomas Granulomas Only a minority of patients Only a minority of patients

Epidemiology & Genetics - IBD M=F M=F Increased risk Increased risk Turners, Hermansky-Pudlak, GSD type 1B, Leukocyte adhesion Turners, Hermansky-Pudlak, GSD type 1B, Leukocyte adhesion First degree relative First degree relative Single greatest risk factor (30 to 100 times) Single greatest risk factor (30 to 100 times) Multiple genetic loci Multiple genetic loci pANCA pANCA 70% UC 70% UC ASCA ASCA 50-60%CD 50-60%CD

Pathogenesis Cause unknown Cause unknown Abnormalities in gastrointestinal immunoregulation Abnormalities in gastrointestinal immunoregulation Cytokines, arachidonic acid metabolites, reactive oxygen intermediates and growth factors Cytokines, arachidonic acid metabolites, reactive oxygen intermediates and growth factors

Diarrhea Factors increase electrolyte secretion Factors increase electrolyte secretion Increased fluid loss Increased fluid loss Loss of bile salts from terminal ileum Loss of bile salts from terminal ileum Malabsorption Malabsorption Bacterial overgrowth Bacterial overgrowth CD CD Exudation of serum proteins and blood Exudation of serum proteins and blood PLE PLE CD CD

Intestinal Manifestations UC UC Bloody diarrhea Bloody diarrhea Proctitis Proctitis May have formed stool May have formed stool Pain with defecation Pain with defecation Both Both Nausea and/or vomiting Nausea and/or vomiting Fever Fever *Know the clinical manifestations and distinguish

Crohn’s Crohn’s Diarrhea Diarrhea 50% 50% Occasionally bloody Occasionally bloody Abdominal pain Abdominal pain More severe More severe Perirectal inflammation Perirectal inflammation 25% 25% Fissure and/or fistula Fissure and/or fistula Aphthous ulcers Aphthous ulcers *Understand that chronic perianal lesions or recurrent aphthous ulcers can be an early sign of CD Intestinal Manifestations

Extraintestinal Manifestations 25-35% 25-35% Directly related to disease activity Directly related to disease activity Unrelated to disease activity Unrelated to disease activity Result from the presence of diseased bowel Result from the presence of diseased bowel Arise from therapy Arise from therapy

Extraintestinal Manifestations Growth Failure Growth Failure 20-30% CD 20-30% CD Multifactorial Multifactorial Chronic undernutrition, steroids, Chronic undernutrition, steroids,cytokines 10% UC 10% UC Prolonged steroids Prolonged steroids Don’t forget delayed puberty Don’t forget delayed puberty *May be a presenting sign *May be a presenting sign *Know the reasons for growth failure in patients with IBD *Know that pts with CD may have GF secondary to decreased caloric intake

Arthritis Arthritis Peripheral Peripheral 10% 10% Larger joints Larger joints Related to active colonic disease Related to active colonic disease Axial Axial Ankylosing spondylitis/Sacroiliitis Ankylosing spondylitis/Sacroiliitis Rare in children Rare in children *Recognize that arthritis may occur in patients with IBD Extraintestinal Manifestations

Skin Skin Pyoderma gangrenosum Pyoderma gangrenosum Erythema nodosum Erythema nodosum Extraintestinal Manifestations

Liver Liver Steatosis Steatosis Elevated enzymes Elevated enzymes Chronic hepatitis Chronic hepatitis Sclerosing cholangitis Sclerosing cholangitis Cholelithiasis Cholelithiasis Acalculous cholecystitis Acalculous cholecystitis Budd-Chiari Syndrome Budd-Chiari Syndrome Extraintestinal Manifestations

Pancreas Pancreas Pancreatitis Pancreatitis Bone Bone Osteopenia Osteopenia Aseptic Necrosis Aseptic Necrosis Eye Eye Uveitis Uveitis Episcleritis Episcleritis Keratitis Keratitis Extraintestinal Manifestations

Urologic Urologic Nephrolithiasis Nephrolithiasis Obstructive hydronephrosis Obstructive hydronephrosis Enterovesical fistula Enterovesical fistula Nephritis Nephritis Amyloidosis Amyloidosis Extraintestinal Manifestations

Hematologic Hematologic Anemia Anemia Iron Iron Folate Folate B12 B12 Autoimmune Autoimmune Thrombocytosis Thrombocytosis Thrombocytopenia Thrombocytopenia Hypercoaguable Hypercoaguable Extraintestinal Manifestations

Diagnosis No substitute for H&P No substitute for H&P Labs Labs Anemia Anemia Most due to iron deficiency Most due to iron deficiency Thrombocytosis Thrombocytosis ESR – 80% CD, 40% UC ESR – 80% CD, 40% UC CRP CRP Sensitive for active disease Sensitive for active disease Low albumin Low albumin Protein loss and malnutrition Protein loss and malnutrition Elevated liver enzymes Elevated liver enzymes pANCA, ASCA pANCA, ASCA

Diagnosis Radiographs Radiographs UGI with SBFT UGI with SBFT CD CD Endoscopy Endoscopy Gross Gross Microscopic Microscopic Complications Complications CT CT Abscess Abscess *Plan the initial evaluation of a patient with suspected IBD

Admit? Severe Colitis Severe Colitis Fever Fever Hypoalbumnemia Hypoalbumnemia Anemia Anemia >5 bloody stools/day >5 bloody stools/day Bowel rest, TPN, IV steroids and careful monitoring Bowel rest, TPN, IV steroids and careful monitoring

Management Pharmacologic Pharmacologic Aminosalicylates Aminosalicylates Mesalamine, sulfasalazine Mesalamine, sulfasalazine Mild colonic inflammation Mild colonic inflammation Corticosteroids Corticosteroids Prednisone, budesonide Prednisone, budesonide Moderate to severe symptoms Moderate to severe symptoms >5 bloody stools/day, fever, hypoalbuminemia, anemia >5 bloody stools/day, fever, hypoalbuminemia, anemia Goal is to decrease symptoms then change to maintenance therapy Goal is to decrease symptoms then change to maintenance therapy

Management Pharmacologic Pharmacologic Immunomodulators Immunomodulators Azathioprine, 6-MP, methotrexate Azathioprine, 6-MP, methotrexate Steroid dependant or refractory Steroid dependant or refractory Maintenance Maintenance Biologics Biologics Infliximab Infliximab Steroid dependant or refractory Steroid dependant or refractory Maintenance Maintenance

Management Pharmacologic Pharmacologic Antibiotics Antibiotics Metronidazole, ciprofloxacin Metronidazole, ciprofloxacin Perirectal fistula, abscess Perirectal fistula, abscess Probiotics Probiotics Lactobacillus GG, Saccharomyces boulardii Lactobacillus GG, Saccharomyces boulardii Adjunctive therapy Adjunctive therapy

Management Nutrition Therapy Nutrition Therapy Primary Primary Adjunctive Adjunctive Important for Important for Remission Remission Chronic undernutrition Chronic undernutrition Growth failure Growth failure

Management Surgical Therapy Surgical Therapy Uncontrolled GI bleeding Uncontrolled GI bleeding Bowel perforation Bowel perforation Obstruction Obstruction Unacceptable medication toxicity Unacceptable medication toxicity Intractability Intractability Growth failure Growth failure Some perirectal disease Some perirectal disease Cancer Cancer

Prognosis UC UC 70% remission in 3 months 70% remission in 3 months 50% remission for 1 year 50% remission for 1 year 10-26% colectomy within 5 years 10-26% colectomy within 5 years 70% likelihood of severe disease if proctitis present 70% likelihood of severe disease if proctitis present

Prognosis CD CD 1% will not have at least one relapse 1% will not have at least one relapse Ileocolitis Ileocolitis Responds poorly to medical therapy Responds poorly to medical therapy Greater need for surgery Greater need for surgery 70% will have surgery within years of diagnosis 70% will have surgery within years of diagnosis Cancer Cancer Colitis >10 y and extent Colitis >10 y and extent Sclerosing cholangitis Sclerosing cholangitis